rs1014527

Positions:

• chr14-90604444-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010854.2(TTC7B):​c.1966+6298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,174 control chromosomes in the GnomAD database, including 575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.080 (575 hom., cov: 33)
• Consequence: TTC7B NM_001010854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660

Genes affected

TTC7B (HGNC:19858): (tetratricopeptide repeat domain 7B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC7B	NM_001010854.2	c.1966+6298G>A		intron_variant		ENST00000328459.11
TTC7B	NM_001320421.2	c.1661-1141G>A		intron_variant
TTC7B	NM_001401365.1	c.2129-1141G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC7B	ENST00000328459.11	c.1966+6298G>A		intron_variant		1	NM_001010854.2	P1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12131 AN: 152056 Hom.: 576 Cov.: 33

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.0645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0798 AC: 12142 AN: 152174 Hom.: 575 Cov.: 33 AF XY: 0.0783 AC XY: 5825 AN XY: 74408

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.0597

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.0596

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0907 Hom.: 874

Bravo AF: 0.0767

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1014527; hg19: chr14-91070788;